Computational biology and bioinformatics articles within Nature Communications

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  • Article
    | Open Access

    Statistical fine-mapping to pinpoint likely causal variants in a genomic region is complicated by linkage disequilibrium (LD). Here, Asimit et al. compare stepwise and stochastic approaches to fine-mapping and propose a Bayesian multinomial stochastic search method which they apply to six immune-mediated diseases.

    • Jennifer L. Asimit
    • , Daniel B. Rainbow
    •  & Chris Wallace

  • Article
    | Open Access

    Interactions between protein and RNA occur on a large scale, and are often studied from a proteincentric point of view. Here the authors show that the number and strength of RNA-protein interactions correlate with the amount of RNA structure, which impacts the biological activity of the transcript.

    • Natalia Sanchez de Groot
    • , Alexandros Armaos
    •  & Gian Gaetano Tartaglia

  • Article
    | Open Access

    Tissue- and cell type-specific information helps to interpret findings from genome-wide association studies. Here, the authors leverage multiple single cell expression datasets to infer cell type specificity of traits.

    • Kyoko Watanabe
    • , Maša Umićević Mirkov
    •  & Danielle Posthuma

  • Article
    | Open Access

    In the ovary, follicular degeneration occurs after folliculogenesis, with one dominant follicle reaching maturity every month. Here, by performing single cell RNA-seq of adult human follicles, the authors identify subclasses of granulosa and theca cell lineages, which correlate with the growth or degeneration of the follicles.

    • X. Fan
    • , M. Bialecka
    •  & S. M. Chuva de Sousa Lopes

  • Article
    | Open Access

    Sequencing of newly synthesised RNA can reveal the transcriptional dynamics in a population of cells. Here the authors develop NASC-seq to bring this sensitivity and temporal resolution to single-cell analysis.

    • Gert-Jan Hendriks
    • , Lisa A. Jung
    •  & Rickard Sandberg

  • Article
    | Open Access

    Membrane proteins have been implicated in cancers, but studying the downstream effects of their perturbation remains challenging. Here, the authors map the membrane protein-regulated network of 15 cancers, a resource for prognostic biomarker development and druggable target identification.

    • Chun-Yu Lin
    • , Chia-Hwa Lee
    •  & Jinn-Moon Yang

  • Article
    | Open Access

    Alcoholic hepatitis, a common cause of liver failure, lacks effective treatment. Here, the authors show altered hepatic HNF4a isoform expression and hypermethylation of its target genes in patients. HNF4a dysregulation is improved in vitro by TGFb or PPARg modulation suggesting potential therapeutic avenues.

    • Josepmaria Argemi
    • , Maria U. Latasa
    •  & Ramon Bataller

  • Comment
    | Open Access

    Infectious disease modeling has played a prominent role in recent outbreaks, yet integrating these analyses into public health decision-making has been challenging. We recommend establishing ‘outbreak science’ as an inter-disciplinary field to improve applied epidemic modeling.

    • Caitlin Rivers
    • , Jean-Paul Chretien
    •  & Simon Pollett

  • Article
    | Open Access

    The transcriptomic profile of tumour-adjacent cells provides important information about tumour context but its clinical utility is unclear. Here, in breast cancer, Fox et al. show that the mRNA abundances of tumour and tumour-adjacent cells hold prognostic information.

    • Natalie S. Fox
    • , Syed Haider
    •  & Paul C. Boutros

  • Article
    | Open Access

    Fourier ring correlation (FRC) analysis is commonly used in fluorescence microscopy to measure effective image resolution. Here, the authors demonstrate that FRC can also be leveraged in blind image restoration methods, such as image deconvolution.

    • Sami Koho
    • , Giorgio Tortarolo
    •  & Giuseppe Vicidomini

  • Article
    | Open Access

    Sequencing platforms, such as Oxford Nanopore or Pacific Biosciences generate long-read data that preserve long-range genomic information but have high error rates. Here, the authors develop MetaMaps, a computational tool for strain-level metagenomic assignment and compositional estimation using long reads.

    • Alexander T. Dilthey
    • , Chirag Jain
    •  & Adam M. Phillippy

  • Article
    | Open Access

    The Scalable Precision Medicine Oriented Knowledge Engine (SPOKE) is a heterogeneous knowledge network that integrates information from 29 public databases. Here, Nelson et al. extend SPOKE to embed clinical data from electronic health records to create medically meaningful barcodes for each medical variable.

    • Charlotte A. Nelson
    • , Atul J. Butte
    •  & Sergio E. Baranzini

  • Article
    | Open Access

    The directions of most human protein-protein interactions (PPIs) remain unknown. Here, the authors use cancer genomic and drug response data to infer the direction of signal flow in the human PPI network and show that the directed network improves drug target and cancer driver gene prioritization.

    • Dana Silverbush
    •  & Roded Sharan

  • Article
    | Open Access

    Core regulatory transcription factors are usually regulated by cell-type specific super enhancers (SEs). Here, the authors screen for chemical probes able to distinguish between SE-driven and promoter-driven transcription and find that histone deacetylases are selectively required for core regulatory transcription.

    • Berkley E. Gryder
    • , Lei Wu
    •  & Javed Khan

  • Article
    | Open Access

    Bulk RNA-seq data harbors valuable information about gene expression levels from different cell types in tissue samples. Here, the authors develop DWLS, a computational method for estimating cell-type composition of bulk data by leveraging single-cell RNA-seq-derived cell-type signatures.

    • Daphne Tsoucas
    • , Rui Dong
    •  & Guo-Cheng Yuan

  • Article
    | Open Access

    Single-nucleus RNA-seq enables interrogation of complex tissues but is limited due to batch effects and processing costs. Here the authors use barcoded antibodies against the nuclear pore complex to label nuclei from distinct samples, and develop a computational tool to assign the sample of origin.

    • Jellert T. Gaublomme
    • , Bo Li
    •  & Aviv Regev

  • Article
    | Open Access

    KRASG12V and BRAFV600E are oncogenic mutations that activate ERK signalling. Here, the authors use single cell analysis in intestinal organoids and show that BRAFV600E activates ERK in all intestinal cell types, while KRASG12V induces ERK activation in only a subset of cells, depending on cell differentiation state.

    • Raphael Brandt
    • , Thomas Sell
    •  & Markus Morkel

  • Article
    | Open Access

    A genetic diagnosis remains unattainable for many individuals with a rare disease because of incomplete knowledge about the genetic basis of many diseases. Here, the authors present the web-based tool GADO (GeneNetwork Assisted Diagnostic Optimization) that uses public RNA-seq data for prioritization of candidate genes.

    • Patrick Deelen
    • , Sipko van Dam
    •  & Lude Franke

  • Article
    | Open Access

    The authors present an extensive profile of host transcriptional respones to a diverse group of pathogens and allergens. In doing so, they identify TH1, type I IFN, TH17, and TH2 responses, that underlie each immune response in both the blood and lung, which represents a global profile of host-pathogen immune responses.

    • Akul Singhania
    • , Christine M. Graham
    •  & Anne O’Garra

  • Article
    | Open Access

    Clinical and molecular heterogeneity of ulcerative colitis presents unresolved challenges to identify predictive biomarkers of response to therapies. Here, the authors combine mouse colitis time course with patient biopsy transcriptomes, achieving unsupervised clustering of UC patients correlating with therapeutic outcomes in independent data sets.

    • Paulo Czarnewski
    • , Sara M. Parigi
    •  & Eduardo J. Villablanca

  • Article
    | Open Access

    Most morphological visualization platforms are not designed to share research data, or are limited to data visualization. Here the authors present MorphoNet, an open-source, web-based tool for interactive visualization and sharing of complex morphodynamic datasets, onto which users can project their own data.

    • Bruno Leggio
    • , Julien Laussu
    •  & Emmanuel Faure

  • Article
    | Open Access

    The role of gene expression noise in the evolution of drug resistance in mammalian cells is unclear. Here, by uncoupling noise from mean expression of a drug resistance gene in CHO cells the authors show that noisy expression aids adaptation to high drug levels, but delays it at low drug levels.

    • Kevin S. Farquhar
    • , Daniel A. Charlebois
    •  & Gábor Balázsi

  • Article
    | Open Access

    The genetic and pathogenetic basis of heart failure is incompletely understood. Here, the authors present a high-fidelity tissue collection from rapidly preserved failing and non-failing control hearts which are used for eQTL mapping and network analysis, resulting in the prioritization of PPP1R3A as a heart failure gene.

    • Pablo Cordero
    • , Victoria N. Parikh
    •  & Euan A. Ashley

  • Article
    | Open Access

    Antibiotics targeting cell wall synthesis display an unexplained gap between in vivo efficacy and in vitro binding affinity for their target. Here, Piepenbreier et al. develop a model for bacterial cell wall biosynthesis, show how it is affected by antibiotics, and use it to predict in vivo efficacy of antibiotics.

    • Hannah Piepenbreier
    • , Angelika Diehl
    •  & Georg Fritz

  • Article
    | Open Access

    Volume electron microscopy data of brain tissue can tell us much about neural circuits, but increasingly large data sets demand automation of analysis. Here, the authors introduce cellular morphology neural networks and successfully automate a range of morphological analysis tasks.

    • Philipp J. Schubert
    • , Sven Dorkenwald
    •  & Joergen Kornfeld

  • Article
    | Open Access

    Metabolic rewiring is a feature of many cancers. Here, the authors combine control theory and flux correlation analysis to study the transition of healthy metabolic networks to cancer states, and find that cancer metabolism is characterized by more streamlined flux distributions.

    • Jean-Marc Schwartz
    • , Hiroaki Otokuni
    •  & Jose C. Nacher

  • Article
    | Open Access

    Most microbiome studies make conclusions based on changes in relative abundance of taxa, inferred from sequencing data. Here, the authors highlight common pitfalls in comparing relative abundance across samples, and identify solutions that reveal microbial changes without the need to estimate total microbial load.

    • James T. Morton
    • , Clarisse Marotz
    •  & Rob Knight

  • Article
    | Open Access

    The oomycete Bremia lactucae is a highly variable pathogen that causes lettuce downy mildew. Here, the authors generate a high-quality genome assembly for B. lactucae, detect a high prevalence of heterokaryosis, and investigate its pathogenic consequences.

    • Kyle Fletcher
    • , Juliana Gil
    •  & Richard Michelmore

  • Article
    | Open Access

    Chromatin is folded into Topologically Associating domains (TADs), with the organization and folding hierarchy of the TADs being highly dynamic. Here the authors develop a parsimonious randomly cross-linked (RCL) polymer model that maps high frequency encounters present in Hi-C data within and between TADs and reconstruct TADs across cell differentiation, revealing local chromatin re-organization.

    • O. Shukron
    • , V. Piras
    •  & D. Holcman

  • Article
    | Open Access

    The brain stores memories through a set of neurons known as engram cells. Here, the authors show that engram cells in the mouse hippocampus are organized into sub-ensembles representing distinct pieces of information, which are then orchestrated to constitute an entire memory.

    • Khaled Ghandour
    • , Noriaki Ohkawa
    •  & Kaoru Inokuchi

  • Article
    | Open Access

    Simulated single cell RNA sequencing data is useful for method development and comparison. Here, the authors developed SymSim, a simulator that explicitly models the main factors of variation in single cell data.

    • Xiuwei Zhang
    • , Chenling Xu
    •  & Nir Yosef

  • Article
    | Open Access

    XFEL radiation is providing new opportunities for probing biological systems. Here the authors perform nanoscale x-ray imaging of microtubules with helical symmetry, by using imaging sorting and reconstruction techniques.

    • Gisela Brändén
    • , Greger Hammarin
    •  & Richard Neutze

  • Article
    | Open Access

    Prediction of face from DNA followed by matching to facial images has been proposed for forensic applications. Here, Sero et al. present a different approach that can establish facial identity from DNA without directly predicting the face but is based on classifying given faces by individual DNA-encoded traits.

    • Dzemila Sero
    • , Arslan Zaidi
    •  & Peter Claes

  • Article
    | Open Access

    Protein degradation in clinical samples is largely unexplored. Here, the authors analyze the transcriptome and proteome of clinical tissue samples and develop an algorithm to assess protein degradation, showing that protein degradation is negligible in most tissue samples and does not correlate with transcript degradation.

    • Wenguang Shao
    • , Tiannan Guo
    •  & Ruedi Aebersold

  • Article
    | Open Access

    Human Hematopoietic stem and progenitor cells (HSPCs) are commonly defined by CD34 expression. Here, the authors map single-cell RNA states both inside and outside the CD34 compartment, uncovering previously unappreciated branchpoints and validating CD164 as an efficient marker for early HSPCs.

    • Danilo Pellin
    • , Mariana Loperfido
    •  & Luca Biasco

  • Article
    | Open Access

    Diagnostic filtering is an important step to analyze the functional and clinical significance of the large number of genetic variants identified from next-generation genome sequencing data. Here, the authors develop a flexible and scalable system for diagnostic filtering of genetic variants using G2P with Ensembl VEP.

    • Anja Thormann
    • , Mihail Halachev
    •  & David R. FitzPatrick

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